v-fps causes transformation by inducing tyrosine phosphorylation and activation of the PDGFβ receptor

Abstract

The v-fps oncogene encodes an activated tyrosine kinase which is capable of transforming fibroblasts. In this report, we provide evidence that within a few minutes of activation of the tyrosine kinase activity of v-Fps, tyrosine phosphorylation of the platelet derived growth factor (PDGF) β receptor is observed. Further, sustained expression of activated v-Fps results in a down-regulation of the PDGF receptor both at the level of the mRNA (4–8-fold), but even more markedly at the level of the receptor protein (>100-fold). The kinase activity of the v-Fps oncoprotein was found to be required for both the induction of PDGF receptor tyrosine phosphorylation and ultimately the reduced receptor protein levels. Tyrosine phosphorylation of a kinase inactive PDGF receptor was also demonstrated in cells which also express v-fps, but this was not sufficient to induce transformation. Only cells expressing both v-fps and a wild type PDGF receptor were able to form colonies in soft agar. These findings suggest that wild type v-fps may use tyrosine phosphorylation of the PDGFβ receptor to constitutively activate the kinase activity of the receptor, resulting in a sustained proliferative signal and fibroblast transformation.

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Correspondence to Deborah H Anderson.

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Anderson, D., Ismail, P. v-fps causes transformation by inducing tyrosine phosphorylation and activation of the PDGFβ receptor. Oncogene 16, 2321–2331 (1998). https://doi.org/10.1038/sj.onc.1201780

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Keywords

  • Fps/Fes
  • PDGFβ receptor
  • down-regulation
  • tyrosine phosphorylation

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